This invention relates generally to methods of cancer therapy and particularly the use lipoic acid as a therapeutic agent administered in combination with ascorbic acid. Ascorbate has been shown to be selectively toxic toward tumor cells, but at doses that are too high to be achieved clinically. Both lipoic acid and its water-soluble sodium salt enhance the efficacy of sodium ascorbate against three-dimensional in vitro tumors and in mouse tumors. These agents can be administered safely to patients, and in preliminary trials have been shown to stabilize or resolve disease.
The most common methods currently in use for the treatment of cancer include surgery, radiation therapy, and chemotherapy. While these therapies are successful for some forms of the disease, they are far from universally successful in curing cancer. Moreover, traditional therapeutic regimens often cause adverse side effects such as nausea, vomiting, cardiac toxicity, bone marrow suppression, and secondary cancer. Vitamin C (ascorbic acid, ascorbate) has been proposed as an alternative to chemotherapy or as an adjuvant to lessen side effects associated with it. (For the purposes of this application, a reference to ascorbic acid includes the anionic component, ascorbate whether as an acid or one of the pharmaceutically acceptable salt thereof, most notably including sodium ascorbate and calcium ascorbate, any of which are included in a reference to xe2x80x9cascorbic acidxe2x80x9d or xe2x80x9cascorbatexe2x80x9d). Ascorbic acid has been thought by some to improve immune response and to prevent tumor spreading by strengthening extracellular matrix, but these theories have not as yet been conclusively proven. Clinical trials with ascorbate at doses on the order of 10 g/day were successful in some cases, but not in others. At very high doses, ascorbic acid is preferentially toxic to tumor cells. This preferential toxicity is understood to relate to the ascorbate mediated production of hydrogen peroxide, which is more toxic to tumor cells due to the lower levels of catalase typically present in tumor cells as compared to normal cells. High dose intravenous ascorbate has thus been suggested for the treatment of cancer, as described in U.S. Pat. No. 5,639,787.
Critical to the use of high dose intravenous ascorbate as an anti-cancer agent is the ability to clinically achieve plasma ascorbate levels sufficient to kill tumor cells. Previous measurements of ascorbate plasma levels following intravenous infusion demonstrate concentrations greater than those needed to kill tumor cells grown in monolayer cultures in vitro. However, much higher levels of ascorbate are required to kill tumor cells grown as three-dimensional in vitro tumors. Using the hollow fiber xe2x80x9csolidxe2x80x9d tumor model, it has been observed that ascorbate concentrations in excess of 500 mg/dL may be required to effectively treat tumors. Currently, the maximum plasma ascorbic acid concentration generally achievable in humans by intravenous infusion is roughly 500 mg/dL, a peak level that drops off sharply over a relatively short period of time. Although ascorbate is relatively innocuous to human patients, the need for higher plasma concentrations demonstrates a need either to safely raise effective plasma levels of ascorbate or to increase the cytotoxic effectiveness of ascorbate toward cancer cells to decrease the required dosage.
One object of the invention is to provide a method for treating cancer by administering lipoic acid and/or a water soluble salt of lipoic acid. Preferably the lipoic acid is administered at 100-1000 mg/day. More preferably at 300-600 mg/day.
A further object of the invention is to provide a method for treating cancer wherein the lipoic acid or combined therapy is used in combination with another therapy. Preferably the lipoic acid is used in combination with ascorbic acid (vitamin C). Preferably the ascorbic acid is administered intravenously at 15-700 g/week, more preferably 50-200 g/week. The preferred ratio of ascorbic acid to lipoic acid is from about 1:1 to about 3500:1, more preferably from about 10:1 to about 100:1.
A further object of the invention is to provide a pharmaceutical composition for treating cancer in a human or other animal comprising lipoic acid and ascorbic acid in an effective dose. The preferred ratio of ascorbic acid to lipoic acid is from about 1:1 to about 3500:1, more preferably from about 10:1 to about 100:1. Preferably the dose of ascorbate is 2-250 g per infusion per day. Preferably the concentration of lipoic acid is 100-1000 mg.